Clinical and Translational Oncology

, Volume 19, Issue 1, pp 12–20 | Cite as

Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma

  • P. Jiménez-FonsecaEmail author
  • J. M. Gómez Saez
  • J. Santamaria Sandi
  • J. Capdevila
  • E. Navarro Gonzalez
  • C. Zafon Llopis
  • T. Ramón y Cajal Asensio
  • G. Riesco-Eizaguirre
  • E. Grande
  • J. C. Galofré
Review Article


Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years.


Anaplastic thyroid carcinoma Poorly differentiated thyroid carcinoma Genetic abnormalities Distant metastases 



The Board of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition (SEEN) and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology (SEOM) staff whose support made this review possible.

Conflict of interest

The authors have nothing to disclose.


  1. 1.
    Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998;338:297–306.CrossRefPubMedGoogle Scholar
  2. 2.
    Zivaljevic V, Slijepcevic N, Paunovic I, Diklic A, Kalezic A, Marinkovic J, et al. Risk factors for anaplastic thyroid cancer. Int J Endocrinol. 2014;2014:815070.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Gómez Sáez JM, Jiménez-Fonseca P, Santamaría Sandi J, Capdevila Castillón J, Navarro González E, et al. Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma. Endocrinol Nutr. 2015;62:e15–22.CrossRefPubMedGoogle Scholar
  4. 4.
    Ain KB. Anaplastic thyroid carcinoma: behavior, biology, and therapeutic approaches. Thyroid. 1998;8:715–26.CrossRefPubMedGoogle Scholar
  5. 5.
    Besic N, Gazic B. Sites of metastases of anaplastic thyroid carcinoma: autopsy findings in 45 cases from a single institution. Thyroid. 2013;23:909–13.CrossRefGoogle Scholar
  6. 6.
    Gómez Sáez JM. Perspectivas actuales en el carcinoma anaplásico de tiroides. In: Gómez Sáez JM, editor. Cáncer de Tiroides: Presente y Futuro. Barcelona: Elsevier; 2014. p. 273–86.Google Scholar
  7. 7.
    Konturek A, Barczynski M, Stopa M, Nowak W. Trends in prevalence of thyroid cancer over three decades: a retrospective cohort study of 17,526 surgical patients. World J Surg. 2016;40(3):538–44.CrossRefPubMedGoogle Scholar
  8. 8.
    Haddad RI, Lydiatt WM, Ball DW, Busaidy NL, Byrd D, Callender G, et al. Anaplastic thyroid carcinoma, version 2.2015. J Natl Compr Cancer Netw. 2015;13:1140–50.Google Scholar
  9. 9.
    Sera N, Ashizawa K, Ando T, Ide A, Abe Y, Usa T, et al. Anaplastic changes associated with p53 gene mutation in differentiated thyroid carcinoma after insufficient radioactive iodine (131I) therapy. Thyroid. 2000;10:975–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Liu D, Xing M. Potent inhibition of thyroid cancer cells by the MEK inhibitor PD 0325901 and its potentiation by suppression of the PI3K and NF-kappaB pathways. Thyroid. 2008;18:853–64.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Nikiforova MN, Nikiforov YE. Molecular diagnostics and predictors in thyroid cancer. Thyroid. 2009;19:1351–61.CrossRefPubMedGoogle Scholar
  12. 12.
    Valeria C, Giovanni Z, Giuseppe P, Pierina P, Angela C, Vito R, et al. Multiple pluripotent stem cell markers in human anaplastic thyroid cancer: the putative upstream role of SOX2. Thyroid. 2012;7:15–26.Google Scholar
  13. 13.
    Griffith OL, Melck A, Montero-Conde C, Martín-Campos JM, Lerma E, Gimenez G, et al. Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers. J Clin Oncol. 2006;24:5043–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Onda M, Emi M, Yoshida A, Miyamoto S, Akaishi J, Asaka S, et al. Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25344 genes. Endocr Relat Cancer. 2004;11:843–54.CrossRefPubMedGoogle Scholar
  15. 15.
    Montero-Conde C, Martín-Campos JM, Lerma E, Giménez G, Martínez-Guitarte JL, Combalía N, et al. Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information. Oncogene. 2008;2:1554–61.CrossRefGoogle Scholar
  16. 16.
    Fuziwara CS, Kimura ET. MicroRNA deregulation in anaplastic thyroid cancer biology. Int J Endocrinol. 2014;2014:1–8.CrossRefGoogle Scholar
  17. 17.
    Reeb AN, Li W, Sewell W, Marlow LA, Tun HW, Smallridge RC, et al. S100A8 is a novel therapeutic target for anaplastic thyroid carcinoma. J Clin Endocrinol Metab. 2015;100:E232–42.CrossRefPubMedGoogle Scholar
  18. 18.
    Zimmermann MB, Galetti V. Iodine intake as a risk factor for thyroid cancer: a comprehensive review of animal and human studies. Thyroid Res. 2015;18(8):8.CrossRefGoogle Scholar
  19. 19.
    Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley JD, Burman KD, for the American Thyroid Association, et al. Anaplastic thyroid cancer guidelines taskforce American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2012;22:1004–139.CrossRefGoogle Scholar
  20. 20.
    Bogsrud TV, Karantanis D, Nathan MA, Mullan VP, Wiseman GA, Kasperbauer JL, et al. 18F-FDG PET in the management of patients with anaplastic thyroid carcinoma. Thyroid. 2008;18:713–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Smallridge RC. Approach to the patient with anaplastic thyroid carcinoma. J Clin Endocrinol Metab. 2012;97:2566–72.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Treglia G, Annunziata S, Muoio B, Salvatori M, Ceriani L, Giovanella L. The role of fluorine-18-fluorodeoxyglucose positron emission tomography in aggressive histological subtypes of thyroid cancer: an overview. Int J Endocrinol. 2013;2013:856189.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, et al. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol. 2007;31:1256–64.CrossRefPubMedGoogle Scholar
  24. 24.
    Burman KD. Is poorly differentiated thyroid cancer poorly characterized? J Clin Endocrinol Metab. 2014;99:1167–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Akaishi J, Sugino K, Kitagawa W, Nagahama M, Kameyama K, Shimizu K, et al. Prognostic factors and treatment outcomes of 100 cases of anaplastic thyroid carcinoma. Thyroid. 2011;21:1183–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Sugitani I, Miyauchi A, Sugino K, Okamoto T, Yoshida A, Suzuki S. Prognostic factors and treatment outcomes for anaplastic thyroid carcinoma: ATC Research Consortium of Japan cohort study of 677 patients. World J Surg. 2012;36:1247–54.CrossRefPubMedGoogle Scholar
  27. 27.
    Wein RO, Weber RS. Anaplastic thyroid carcinoma: palliation or treatment? Curr Opin Otolaryngol Head Neck Surg. 2011;19:113–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Keutgen XM, Sadowski SM, Kebebew E. Management of anaplastic thyroid cancer. Gland Surg. 2015;4:44–51.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Chiacchio S, Lorenzoni A, Boni G, Rubello D, Elisei R, Mariani G. Anaplastic thyroid cancer: prevalence, diagnosis and treatment. Minerva Endocrinol. 2008;33:341–57.PubMedGoogle Scholar
  30. 30.
    Pudney D, Lau H, Ruether JD, Falck V. Clinical experience of the multimodality management of anaplastic thyroid cancer and literature review. Thyroid. 2007;17:1243–50.CrossRefPubMedGoogle Scholar
  31. 31.
    Goffreddo P, Thomas SM, Adam MA, Sosa JA, Roman SA. Impact of timeliness of resection and thyroidectomy margin status on survival for patients with anaplastic thyroid cancer: an analysis of 335 cases. Ann Surg Oncol. 2015;22:4166–74.CrossRefGoogle Scholar
  32. 32.
    Sherman EJ, Lim SH, Ho AL, Ghossein RA, Fury MG, Shaha AR, et al. Concurrent doxorubicin and radiotherapy for anaplastic thyroid cancer: a critical re-evaluation including uniform pathologic review. Radiother Oncol. 2011;101:425–30.CrossRefPubMedGoogle Scholar
  33. 33.
    Wang Y, Tsang R, Asa S, Dickson B, Arenovich T, Brierley J. Clinical outcome of anaplastic thyroid carcinoma treated with radiotherapy of once- and twice-daily fractionation regimens. Cancer. 2006;107:1786–92.CrossRefPubMedGoogle Scholar
  34. 34.
    He X, Li D, Hu C, Wang Z, Ying H, Wu Y. Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma. BMC Cancer. 2014;14:235.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Bhatia A, Rao A, Ang KK, Garden AS, Morrison WH, Rosenthal DI, et al. Anaplastic thyroid cancer: clinical outcomes with conformal radiotherapy. Head Neck. 2010;32:829–36.PubMedGoogle Scholar
  36. 36.
    Sun XS, Sun SR, Guevara N, Fakhry N, Marcy PY, Lassalle S, et al. Chemoradiation in anaplastic thyroid carcinomas. Crit Rev Oncol Hematol. 2013;86:290–301.CrossRefPubMedGoogle Scholar
  37. 37.
    Heron DE, Karimpour S, Grigsby PW. Anaplastic thyroid carcinoma: comparison of conventional radiotherapy and hyperfractionation chemoradiotherapy in two groups. Am J Clin Oncol. 2002;25:442–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Higashiyama T, Ito Y, Hirokawa M, Fukushima M, Uruno T, Miya A, et al. Induction chemotherapy with weekly paclitaxel administration for anaplastic thyroid carcinoma. Thyroid. 2010;20:7–14.CrossRefPubMedGoogle Scholar
  39. 39.
    Sosa JA, Balkissoon J, Lu SP, Langecker P, Elisei R, Jarzab B, et al. Thyroidectomy followed by fosbretabulin (CA4P) combination regimen appears to suggest improvement in patient survival in anaplastic thyroid cancer. Surgery. 2012;152:1078–87.CrossRefPubMedGoogle Scholar
  40. 40.
    Savvides P, Nagaiah G, Lavertu P, Fu P, Wright JJ, Chapman R, et al. Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid. Thyroid. 2013;23:600–4.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Thomas L, Lai SY, Dong W, Feng L, Dadu R, Regone RM, et al. Sorafenib in metastatic thyroid cancer: a systematic review. Oncologist. 2014;19:251–8.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384:319–28.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, et al. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008;26:4708–13.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Pennell NA, Daniels GH, Haddad RI, Ross DS, Evans T, Wirth LJ, et al. A phase II study of gefitinib in patients with advanced thyroid cancer. Thyroid. 2008;18:317–23.CrossRefPubMedGoogle Scholar
  45. 45.
    Ha HT, Lee JS, Urba S, Koenig RJ, Sisson J, Giordano T, et al. A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid. 2010;20:975–80.CrossRefPubMedGoogle Scholar
  46. 46.
    Grande E, Capdevila J, Díez JJ, Longo F, Carrato A. A significant response to sunitinib in a patient with anaplastic thyroid carcinoma. J Res Med Sci. 2013;18:623–5.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Mooney CJ, Nagaiah G, Fu P, Wasman JK, Cooney MM, Savvides PS, et al. Phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid. 2009;19:233–40.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Ain KB, Egorin MJ, DeSimone PA. Treatment of anaplastic thyroid carcinoma with paclitaxel: phase 2 trial using ninety-six-hour infusion. Collaborative Anaplastic Thyroid Cancer Health Intervention Trials (CATCHIT) Group. Thyroid. 2000;10:587–94.CrossRefPubMedGoogle Scholar
  49. 49.
    Smallridge RC, Copland JA, Brose MS, Wadsworth JT, Houvras Y, Menefee ME, et al. Efatutazone, an oral PPAR-γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: results of a multicentre phase 1 trial. J Clin Endocrinol Metab. 2013;98:2392–400.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Isham CR, Bossou AR, Negron V, Fisher KE, Kumar R, Marlow L, et al. Pazopanib enhances paclitaxel-induced mitotic catastrophe in anaplastic thyroid cancer. Sci Transl Med. 2013;5:166ra3.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Sosa JA, Elisei R, Jarzab B, Balkissoon J, Lu SP, Bal C, et al. Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma. Thyroid. 2014;24:232–40.CrossRefPubMedGoogle Scholar
  52. 52.
  53. 53.
    Wagle N, Grabiner BC, Van Allen EM, Amin-Mansour A, Taylor-Weiner A, Rosenberg M, et al. Response and acquired resistance to everolimus in anaplastic thyroid cancer. N Engl J Med. 2014;371:1426–33.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Marotta V, Sciammarella C, Vitale M, Colao A, Faggiano A. The evolving field of kinase inhibitors in thyroid cancer. Crit Rev Oncol Hematol. 2015;93:60–73.CrossRefPubMedGoogle Scholar
  55. 55.
    Shinohara S, Kikuchi M, Naito Y, Fujiwara K, Hori S, Tona Y, et al. Successful treatment of locally advanced anaplastic thyroid carcinoma by chemotherapy and hyperfractionated radiotherapy. Auris Nasus Larynx. 2009;36:729–32.CrossRefPubMedGoogle Scholar
  56. 56.
    Noguchi H, Yamashita H, Murakami T, Hirai K, Noguchi Y, Maruta J, et al. Successful treatment of anaplastic thyroid carcinoma with a combination of oral valproic acid, chemotherapy, radiation and surgery. Endocr J. 2009;56:245–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Fury MG, Solit DB, Su YB, Rosen N, Sirotnak FM, Smith RP, et al. A phase I trial of intermittent high-dose gefitinib and fixed-dose docetaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2007;59:467–75.CrossRefPubMedGoogle Scholar
  58. 58.
    Hogan T, Jing Jie Yu, Williams HJ, Altaha R, Xiaobing Liang, Qi He. Oncocytic, focally anaplastic, thyroid cancer responding to erlotinib. J Oncol Pharm Pract. 2009;15:111–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Rosove MH, Peddi PF, Glaspy JA. BRAF V600E Inhibition in anaplastic thyroid cancer. N Engl J Med. 2013;368:684–5.CrossRefPubMedGoogle Scholar
  60. 60.
    Lee YJ, Chung JK, Shin JH, Kang JH, Jeong JM, Lee DS, et al. In vitro and in vivo properties of a human anaplastic thyroid carcinoma cell line transfected with the sodium iodide symporter gene. Thyroid. 2004;14:889–95.CrossRefPubMedGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2016

Authors and Affiliations

  • P. Jiménez-Fonseca
    • 1
    Email author
  • J. M. Gómez Saez
    • 2
  • J. Santamaria Sandi
    • 3
  • J. Capdevila
    • 4
  • E. Navarro Gonzalez
    • 5
  • C. Zafon Llopis
    • 6
  • T. Ramón y Cajal Asensio
    • 7
  • G. Riesco-Eizaguirre
    • 8
  • E. Grande
    • 9
  • J. C. Galofré
    • 10
  1. 1.Medical Oncology ServiceHospital Universitario Central de AsturiasOviedoSpain
  2. 2.CIBERDEM, Endocrinology and Nutrition ServiceHospital Universitario de BellvitgeBarcelonaSpain
  3. 3.Endocrinology and Nutrition ServiceHospital Universitario de CrucesVizcayaSpain
  4. 4.Medical Oncology ServiceHospital Universitario de la Vall d’HebronBarcelonaSpain
  5. 5.Endocrinology and Nutrition ServiceHospital Universitario Virgen del RocioSevillaSpain
  6. 6.Endocrinology and Nutrition ServiceHospital Universitario de la Vall d’HebronBarcelonaSpain
  7. 7.Medical Oncology ServiceHospital de la Santa Creu i Sant PauBarcelonaSpain
  8. 8.Endocrinology and Nutrition ServiceHospital Universitario de MóstolesMadridSpain
  9. 9.Medical Oncology ServiceHospital Universitario Ramón y CajalMadridSpain
  10. 10.Endocrinology and Nutrition ServiceClínica Universidad de NavarraPamplonaSpain

Personalised recommendations